Investigating the Potential of Bevacizumab in Other Indications: Metastatic Renal Cell, Non-Small Cell Lung, Pancreatic and Breast Cancer

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Abstract
Bevacizumab (Avastin) has unprecedented survival benefit in patients with metastatic colorectal cancer. Trials are already in progress to investigate the potential of bevacizumab in indications including metastatic renal cell cancer (RCC), non-small cell lung cancer (NSCLC), pancreatic cancer, breast and ovarian cancer. Bevacizumab offers the potential to increase survival without substantially altering the toxicity profile in these tumor types. Bevacizumab has shown activity in patients with refractory metastatic RCC, where progression-free survival (PFS) was significantly longer in patients treated with bevacizumab (10 mg/kg every 2 weeks) than those treated with placebo (hazard ratio=2.55, p<0.001). In addition, combining bevacizumab with erlotinib (Tarceva) has shown a median time to progression of more than 11 months. In NSCLC, a phase II trial revealed that adding bevacizumab to chemotherapy increased therapeutic benefit compared with chemotherapy alone. Adverse events were mild and easily managed, but six patients receiving bevacizumab developed severe hemoptysis. Entry criteria for NSCLC trials have been adjusted to exclude patients with squamous cell histology to try to avoid this issue. Adding bevacizumab (10 mg/kg) to the current standard of care, gemcitabine, in stage IV pancreatic cancer has also shown promising efficacy. Partial responses were seen in 19% of patients, with a further 48% having stable disease. Several ongoing clinical trials are also studying bevacizumab with various chemotherapy and radiotherapy regimens. Bevacizumab combined with carboplatin (Paraplatin)/paclitaxel (Taxol) was further examined in a phase III randomized trial that accrued 878 patients with advanced non-squamous cell NSCLC. Patients given chemotherapy (paclitaxel and carboplatin) plus bevacizumab had a higher response rate, longer PFS and an increase in survival compared with patients on chemotherapy alone. Both regimens were generally well tolerated. Bevacizumab has also shown activity in patients with metastatic breast cancer. In 715 patients, a significant, 2-fold increase in response rate was observed in patients receiving bevacizumab plus paclitaxel compared with paclitaxel alone. Median PFS was also significantly increased (p<0.001). Bevacizumab has the potential to provide significant efficacy benefits for patients with metastatic RCC, NSCLC, pancreatic cancer, and other tumor types when used first line in combination with standard therapy.